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CD3−CD56+dim natural killer (NK) cells, which are cytotoxic against virally infected cells, may be important in hepatitis C virus (HCV)-infected patients who are successfully treated with pegylated interferon (PEG-IFN)-α. We used flow cytometry to enumerate activated (CD69+) and apoptotic (annexin-V+) dim (CD3−CD56+dim) and bright (CD3−CD56+bright) NK cells obtained from HCV-infected patients before treatment (n = 16) and healthy controls (n = 15) in the absence and presence of pegylated interferon (PEG-IFN)-α-2b. A subset of HCV-infected patients, subsequently treated with PEG-IFN-α-2b in vivo, was determined to have a sustained virological response (SVR, n = 6) or to not respond (NR) to treatment (n = 5). In the absence of IFN, activated dim (CD3−CD56+dim CD69+) NK cells were significantly decreased (P = 0·04) while activated apoptotic dim (CD3−CD56+dimCD69+annexin-V+) NK cells tended to be increased (P = 0·07) in SVR patients compared with NR patients. Activated bright (CD3−CD56+brightCD69+) and activated apoptotic bright (CD3−CD56+brightCD69+annexin-V+) NK cells were significantly correlated (P = 0·02 and P = 0·01, respectively) with increasing hepatic inflammation. These findings suggest that in the absence of PEG-IFN, activated dim (CD3−CD56+dimCD69+) NK cell turnover may be enhanced in SVR compared with NR patients and that activated bright (CD3−CD56+brightCD69+) NK cells may play a role in liver inflammation.